Childhood asthma is associated with polymorphic markers of PROC on 2q14 in addition to 17q21 locus.
| Autor: | Chan WC; Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong., Sy HY, Kong AP, Wong CK, Tse LY, Hon KL, Chan JC, Wong GW, Leung TF |
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| Jazyk: | angličtina |
| Zdroj: | Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology [Pediatr Allergy Immunol] 2015 Mar; Vol. 26 (2), pp. 173-80. |
| DOI: | 10.1111/pai.12336 |
| Abstrakt: | Background: Childhood asthma is caused by both genetic and environmental factors. The first genomewide association study (GWAS) for asthma revealed putative candidates on nine chromosomal regions in Caucasians, with 17q21 locus being the most widely replicated one. However, there was no replication study for the other loci. This study investigated genetic associations between childhood asthma and autosomal single nucleotide polymorphisms (SNPs) on eight loci reported in the first GWAS among Hong Kong Chinese. Methods: 510 asthmatic children and 510 non-allergic controls were recruited. 110 tagging SNPs selected based on r(2 ) ≥ 0.80 and minor allele frequency ≥0.05 for Han Chinese among all SNPs located 50-kb upstream and downstream of significant autosomal SNPs were genotyped by TaqMan allelic discrimination assays. Transcription factor binding of SNPs was determined by electrophoretic mobility shift assay (EMSA). Results: Asthma was significantly associated with SNPs on 17q21 and 2q14 loci. Twelve SNPs on 17q21 were associated with asthma, with rs6503527 being the most significant SNP. Five SNPs of protein C gene (PROC) on 2q14 were associated with asthma, with rs6755028 being the most significant SNP. Plasma protein C concentrations were higher in asthmatic patients than controls, and five PROC SNPs were associated with plasma protein C concentrations. EMSA showed specific differential binding of rs878461 to nuclear extracts from bronchial epithelial and hepatocarcinoma cell lines. Conclusions: Our findings identify PROC on 2q14 as a novel candidate for childhood asthma and replicate the genetic association for 17q21 locus. Rs878461 of PROC may increase asthma susceptibility by altering transcription factor binding. (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.) |
| Databáze: | MEDLINE |
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